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Cancers (Basel). 2019 Dec 30;12(1). pii: E92. doi: 10.3390/cancers12010092.

Human Tumor-Derived Matrix Improves the Predictability of Head and Neck Cancer Drug Testing.

Author information

1
Department of Oral and Maxillofacial Diseases, Clinicum, Faculty of Medicine, University of Helsinki, 00014 Helsinki, Finland.
2
Translational Immunology Research Program (TRIMM), University of Helsinki, 00014 Helsinki, Finland.
3
Institute for Molecular Medicine Finland (FIMM), University of Helsinki, 00290 Helsinki, Finland.
4
Research Programs Unit, Genome-Scale Biology Program and Medicum, Biochemistry and Developmental Biology, University of Helsinki, 00014 Helsinki, Finland.
5
Biostatistics Consulting, Department of Public Health, University of Helsinki and Helsinki University Hospital, 00014 Helsinki, Finland.
6
Cancer and Translational Medicine Research Unit, University of Oulu, 90014 Oulu, Finland.
7
Department of Otorhinolaryngology-Head and Neck Surgery, Turku University Hospital, University of Turku, 20520 Turku, Finland.
8
Biotech Research and Innovation Center, Department of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark.
9
Medical Research Center, Oulu University Hospital, 90014 Oulu, Finland.
10
Helsinki University Hospital, 00029 Helsinki, Finland.

Abstract

In vitro cancer drug testing carries a low predictive value. We developed the human leiomyoma-derived matrix "Myogel" to better mimic the human tumor microenvironment (TME). We hypothesized that Myogel could provide an appropriate microenvironment for cancer cells, thereby allowing more in vivo-relevant drug testing. We screened 19 anticancer compounds, targeting the epidermal growth factor receptor (EGFR), MEK, and PI3K/mTOR on 12 head and neck squamous cell carcinoma (HNSCC) cell lines cultured on plastic, mouse sarcoma-derived Matrigel (MSDM), and Myogel. We applied a high-throughput drug screening assay under five different culturing conditions: cells in two-dimensional (2D) plastic wells and on top or embedded in Matrigel or Myogel. We then compared the efficacy of the anticancer compounds to the response rates of 19 HNSCC monotherapy clinical trials. Cancer cells on top of Myogel responded less to EGFR and MEK inhibitors compared to cells cultured on plastic or Matrigel. However, we found a similar response to the PI3K/mTOR inhibitors under all culturing conditions. Cells grown on Myogel more closely resembled the response rates reported in EGFR-inhibitor monotherapy clinical trials. Our findings suggest that a human tumor matrix improves the predictability of in vitro anticancer drug testing compared to current 2D and MSDM methods.

KEYWORDS:

clinical trials; drug screening; head and neck cancer; human tumor microenvironment; in vitro 3D

PMID:
31905951
DOI:
10.3390/cancers12010092
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